Pillar 3: Viva Skills Coaching
Pharmaceutical Technical Viva Hub
Review rapid-fire oral technical prompts, model answers, and board advice. Rehearse out loud to eliminate hesitation under interview pressure.
Quality Assurance & cGMP
Topic: CAPA Investigation & Root Cause Analysis
How would you conduct a Corrective and Preventive Action (CAPA) investigation when a finished batch fails its dissolution test?
• Immediate containment
• Phase I lab error verification
• Cross-functional Phase II investigation
• 5-Why root cause analysis
• Effectiveness check
Suggested Model Answer:
1. Containment & Quarantine: Immediately quarantine the affected batch and place ongoing packaging on hold.
2. Lab Investigation (Phase I OOS): Verify analytical integrity—inspect chromatography integration, standard preparation, column log, instrument calibration, and test analyst technique. Confirm whether it is an analytical or manufacturing error.
3. Manufacturing Investigation (Phase II): If lab error is ruled out, assemble an interdisciplinary team (QA, Production, Engineering, QC). Examine Batch Manufacturing Records (BMR), mixing time, granulation moisture content (LOD), compression force, and excipient lot variations.
4. Root Cause Determination: Utilize systematic tools like the 5-Why analysis or Fishbone (Ishikawa) diagram to identify the true root cause rather than symptoms.
5. Corrective Action: Address the immediate batch (reject/reprocess if validated) and calibrate/service tooling.
6. Preventive Action: Revise SOPs, retrain operators, update equipment preventive maintenance schedules, and monitor subsequent 3 batches for effectiveness verification.
💡 Interview Board Tip:
Always emphasize Phase I lab investigation first before jumping to plant blame. Interviewers look for strict adherence to FDA/MHRA OOS flowcharts.
Industrial Pharmaceutics
Topic: Tablet Tooling Defects (Capping, Sticking, Picking)
What are the main causes of "Tablet Sticking" during compression, and how would you resolve it on the production floor?
• Moisture (LOD)
• Lubrication deficiency
• Punch face wear/polishing
• Cubicle RH control
Suggested Model Answer:
Causes of Tablet Sticking (adhesion of granules to punch faces):
1. Excessive Moisture: Inadequately dried granules (high loss on drying, LOD).
2. Insufficient Lubrication: Inadequate magnesium stearate concentration or poor blending time.
3. Punch Tooling Issues: Scratched, worn, or unpolished punch faces; embossed logos with sharp angles.
4. Environmental Humidity: Relative humidity in the compression cubicle exceeding 45-50% RH for hygroscopic materials.
Remedies:
- Check LOD of granules and return to fluid bed dryer if moisture is out of limits.
- Increase lubricant blending efficiency or adjust magnesium stearate (typically 0.5 - 1.0%).
- Polish punch faces with diamond compound or apply anti-stick coatings (e.g. Chromium Nitride / Teflon).
- Ensure compression cubicle air conditioning maintains <= 40-45% RH.
💡 Interview Board Tip:
Mention both formulation factors (moisture, lubricant) and mechanical/environmental factors (punch polishing, RH).
Instrumental Analysis & QC
Topic: HPLC Troubleshooting: Peak Tailing & Retention Drift
What causes peak tailing in reverse-phase HPLC, and how do you troubleshoot it?
• Residual silanols
• End-capped C18
• Guard column replacement
• pH optimization relative to pKa
Suggested Model Answer:
Primary causes of peak tailing (Asymmetry factor > 1.5):
1. Secondary Silanol Interactions: Basic analytes interacting with residual unreacted acidic silanol (Si-OH) groups on older silica packings.
2. Column Void or Channeling: Settling of stationary phase packing at the column inlet due to pressure shocks or high pH.
3. Column Contamination: Strongly retained matrix components or particulate build-up on the inlet frit.
4. Sample Overload: Injecting sample mass or volume exceeding column capacity.
Troubleshooting steps:
- Use base-deactivated silica (BDS) or end-capped high purity C18 columns.
- Add a mobile phase modifier (such as 0.1% triethylamine or adjust buffer pH below the analyte's pKa to suppress ionization).
- Flush column with strong organic solvents (100% Acetonitrile, Methanol, or IPA) or reverse-flush according to manufacturer specs.
- Replace guard column or check inlet frit.
- Dilute the sample or decrease injection volume.
💡 Interview Board Tip:
Differentiate between physical column void (which causes tailing on all peaks) versus chemical secondary interaction (which affects only basic analytes).
Regulatory Affairs
Topic: CTD Structure & Module 3
Explain the structure of the Common Technical Document (CTD) and why Module 3 is critical for industrial pharmacists.
• 5 Modules structure
• Module 3 is CMC Quality
• 3.2.S and 3.2.P breakdown
• Direct industrial relevance
Suggested Model Answer:
The Common Technical Document (CTD) is an internationally agreed format organized into 5 Modules:
- Module 1: Administrative Information and Prescribing Info (region specific: DGDA, FDA, EMA).
- Module 2: CTD Summaries (Quality Overall Summary, Clinical & Non-clinical overviews).
- Module 3: Quality (Chemistry, Manufacturing, and Controls - CMC).
- Module 4: Non-clinical Study Reports (Toxicology, Pharmacology).
- Module 5: Clinical Study Reports (Human efficacy, safety, bioequivalence).
Why Module 3 is critical for pharmacists:
Module 3 details everything regarding drug substance (3.2.S) and drug product (3.2.P): formula, batch manufacturing formulas, manufacturing process validation, container closure systems, analytical procedure validation, and 6-month accelerated plus real-time stability data. Industrial pharmacists directly generate and verify Module 3 data.
💡 Interview Board Tip:
State the exact module names clearly and emphasize 3.2.S (Drug Substance) and 3.2.P (Drug Product).
Aseptic Manufacturing & Microbiology
Topic: Media Fill Trials & Sterility Assurance
What is a "Media Fill" trial in sterile manufacturing, and what is the allowable contamination limit for 5,000 to 10,000 units filled?
• Aseptic process simulation
• TSB nutrient broth
• 14-day incubation
• Zero growth target
Suggested Model Answer:
A Media Fill (Aseptic Process Simulation - APS) is a trial in which a nutrient growth medium (typically Soybean Casein Digest Medium / TSB) is substituted for the actual drug product and processed through the sterile filling line simulating routine manufacturing conditions (including shift changes, operator interventions, and worst-case line stoppages).
Acceptance Criteria (FDA / PIC/S / WHO):
- Filling < 5,000 units: Zero contaminated units should be detected.
- Filling 5,000 to 10,000 units: 1 contaminated unit should prompt an investigation and consideration of repeating media fill; 2 contaminated units considered revalidation failure.
- Filling > 10,000 units: 1 contaminated unit triggers formal investigation; 2 contaminated units revalidation.
All media fill units are incubated at 20-25°C and 30-35°C for not less than 14 days and inspected for turbidity.
💡 Interview Board Tip:
Mention the growth medium (TSB/SCDM), 14-day dual temperature incubation, and zero-contamination goal.